Safe Scale-Up of Pharmaceutical Manufacturing Processes with Dimethyl Sulfoxide as the Solvent and a Reactant or a Byproduct

Wang, Zhe; Richter, Steven M.; Bellettini, John R.; Pu, Yu‐Ming; Hill, David R.

doi:10.1021/op500260n

Cited by 30 publications

(24 citation statements)

References 9 publications

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“…The oxidation of a 2-hydroxyamide under Moffatt conditions was the last step along the synthesis of the serine protease inhibitor boceprevir (Scheme ). Recently, this oxidation was performed with DMP in ethyl acetate, thus avoiding the displeasing odor of dimethyl sulfide, which represents an important drawback on the industrial scale …”

Section: Oxidative Processes At C(2)mentioning

confidence: 99%

“…69 Recently, this oxidation was performed with DMP in ethyl acetate, 70 thus avoiding the displeasing odor of dimethyl sulfide, which represents an important drawback on the industrial scale. 71 Several methodologies for the oxidation of alcohols with stoichiometric dioxygen by using metal oxides as well as homogeneous or heterogeneous metal complexes as the catalysts have been developed in the last two decades. Furthermore, in recent years the asymmetric variants of the aerobic catalytic processes have attracted a lot of attention.…”

Section: Oxidative Processes At C(2)mentioning

confidence: 99%

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Recent Developments in General Methodologies for the Synthesis of α-Ketoamides

2016

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The α-ketoamide motif is widely found in many natural products and drug candidates with relevant biological activities. Furthermore, α-ketoamides are attractive candidates to synthetic chemists due to the ability of the motif to access a wide range of functional group transformations, including multiple bond-forming processes. For these reasons, a vast array of synthetic procedures for the preparation of α-ketoamides have been developed over the past decades, and the search for expeditious and efficient protocols continues unabated. The aim of this review is to give an overview of the diverse methodologies that have emerged since the 1990s up to the present. The different synthetic routes have been grouped according to the way the α-ketoamide moiety has been created. Thus, syntheses of α-ketoamides proceeding via C(2)-oxidation of amide starting compounds are detailed, as are amidation approaches installing the α-ketoamide residue through C(1)-N bond formation. Also discussed are the methodologies centered on C(1)-C(2) σ-bond construction and C(2)-R/Ar bond-forming processes. Finally, the literature regarding the synthesis of α-ketoamide compounds by palladium-catalyzed double-carbonylative amination reactions is discussed.

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Section: Oxidative Processes At C(2)mentioning

confidence: 99%

Section: Oxidative Processes At C(2)mentioning

confidence: 99%

Recent Developments in General Methodologies for the Synthesis of α-Ketoamides

2016

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“…Previously, the use of DMF that belongs to the second haz ard class as a co-solvent for hydrophobization of metal surfaces with stearic acid was re ported [6]. In contrast, DMSO that belongs to the fourth hazard class is much less toxi [51][52][53] and is even recommended for pharmaceutical applications to provide an accepta ble rate of transdermal drug delivery [54,55]. Therefore, the replacement of DMF with DMSO would help reduce the risks of poisoning, development of oncological disease [56,57], and the impact on the environment if this approach to hydrophobization of the surfaces of metals and alloys were to be used on an industrial scale.…”

Section: Resultsmentioning

confidence: 99%

Regularities of the Formation of a Green Superhydrophobic Protective Coating on an Aluminum Alloy after Surface Modification with Stearic Acid Solutions

Abrashov

Grigoryan

Korshak

et al. 2021

Metals

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It has been shown that solutions of stearic acid in a dimethyl sulfoxide–water binary mixture allow superhydrophobic protective coatings to be created on an aluminum alloy surface with a minimum impact on the environment. The superhydrophobicity and self-cleaning ability of the coating that we developed have been confirmed by measurements of droplet wetting angles and roll-off angles. These properties appear due to the formation of a multimodal micro-rough surface that mainly consists of aluminum stearate. The coatings formed in this manner have been studied by ellipsometry, XPS, and scanning probe microscopy. Their protective ability has been estimated by the “droplet-express” method and in a salt fog chamber. The protective ability of the coating is determined by the DMSO/H2O ratio, the concentration of stearic acid, and the duration and temperature of modification of the aluminum alloy; it is controlled by a competition between the processes of aluminum stearate formation and hydrolysis. It has been shown that adsorption of stearic acid on an aluminum stearate coating increases its permeability and decreases its protective capability. The results presented in this article are useful for optimizing the conditions of applying green superhydrophobic stearate coatings on aluminum alloys in order to achieve a maximum protective effect.

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“…Based on the observations from these experiments, a combination of DMSO and EtOAc was selected for further development and scale-up. 17,18 In a risk assessment exercise prior to the further development and scale-up of the DMSO/EtOAc recrystallization, the risk of forming the methylthiomethyl ester impurity 7 (Figure 4) via a Pummerer rearrangement was highlighted. An authentic sample of methylthiomethyl ester 7 was prepared 7,19,20 and the risk discharged as no methylthiomethyl ester was detected by HPLC analysis.…”

Section: Organic Process Research and Developmentmentioning

confidence: 99%

“…Factors such as solution stability versus temperature were evaluated along with other factors such as filterability, residual solvent content, impurity profile, and particle morphology. Based on the observations from these experiments, a combination of DMSO and EtOAc was selected for further development and scale-up. , …”

Section: Introductionmentioning

confidence: 99%

Process Development toward a Pro-Drug of Buprenorphine

Berrell

Byard²,

Carey

et al. 2019

Org. Process Res. Dev.

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This paper describes the process development conducted toward the multi-kilogram synthesis of a hemiadipic acid pro-drug of buprenorphine. The major challenges were to control the levels of the dibuprenorphine monoadipate impurity and to improve the robustness of the final recrystallization. Modification of the reaction conditions limited the levels of the impurity formed during the reaction, and an additional point of control was introduced, a reslurry with dichloromethane. The solid-state properties of the pro-drug were fully investigated, and extensive polymorph screening was undertaken. An unusual low-temperature endothermic event was observed in the differential scanning calorimetry thermogram. This low-temperature event was further investigated using variable-temperature X-ray powder diffraction and variable-temperature solid-state nuclear magnetic resonance spectroscopy. It was concluded that this event was likely to be associated with a reversible, minor conformational change of the adipate side chain.

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Safe Scale-Up of Pharmaceutical Manufacturing Processes with Dimethyl Sulfoxide as the Solvent and a Reactant or a Byproduct

Cited by 30 publications

References 9 publications

Recent Developments in General Methodologies for the Synthesis of α-Ketoamides

Recent Developments in General Methodologies for the Synthesis of α-Ketoamides

Regularities of the Formation of a Green Superhydrophobic Protective Coating on an Aluminum Alloy after Surface Modification with Stearic Acid Solutions

Process Development toward a Pro-Drug of Buprenorphine

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